The relationship between the auriculotemporal nerve and middle meningeal artery in a sample of the South African population.

BACKGROUND: The interaction between the auriculotemporal nerve and the middle meningeal artery within the infratemporal fossa is vital in the spread of perineural tumours. Knowledge of their morphological and morphometric variations is critical to surgeons approaching the infratemporal fossa. There is a paucity of literature on the relationship between the auriculotemporal nerve and middle meningeal artery in a South African population. Hence, the aim of this study was to document the morphology and morphometry of the auriculotemporal nerve and its relationship to the middle meningeal artery within a South African cohort. MATERIALS AND METHODS: The infratemporal fossae of 32 cadaveric specimens were dissected and the auriculotemporal nerves and middle meningeal arteries were analysed, together with their variations. RESULTS: Nine out of 32 specimens displayed one-root, 14/32 two-root, 7/32 three-root, and 2/32 four-root auriculotemporal nerves. Eighteen auriculotemporal nerves originated from the mandibular nerve, while the rest had at least one communication to the inferior alveolar nerve. The mean distance between the first and second roots of the auriculotemporal nerve was 4.69 mm. There were V-shaped formations found in 23 auriculotemporal nerves. However, the middle meningeal artery only passed through 13/23 V-shapes. The maxillary artery was of a deep course in relation to the lateral pterygoid muscle in 19/32 and superficial in 13/32 of the sample. There were 15 accessory middle meningeal arteries present in 14/32 specimens. The accessory middle meningeal arteries often arose from the middle meningeal artery (46.67%). CONCLUSIONS: The results of this study show a high possibility of variations of the auriculotemporal nerve and middle meningeal artery in the South African population. The variations and interactions should be considered during surgical procedures.

Modulation of nociceptive dural input to the trigeminocervical complex through GluK1 kainate receptors.

Migraine is a common and disabling neurologic disorder, with important psychiatric comorbidities. Its pathophysiology involves activation of neurons in the trigeminocervical complex (TCC). Kainate receptors carrying the glutamate receptor subunit 5 (GluK1) are present in key brain areas involved in migraine pathophysiology. To study the influence of kainate receptors on trigeminovascular neurotransmission, we determined the presence of GluK1 receptors within the trigeminal ganglion and TCC with immunohistochemistry. We performed in vivo electrophysiologic recordings from TCC neurons and investigated whether local or systemic application of GluK1 receptor antagonists modulated trigeminovascular transmission. Microiontophoretic application of a selective GluK1 receptor antagonist, but not of a nonspecific ionotropic glutamate receptor antagonist, markedly attenuated cell firing in a subpopulation of neurons activated in response to dural stimulation, consistent with selective inhibition of postsynaptic GluK1 receptor-evoked firing seen in all recorded neurons. In contrast, trigeminovascular activation was significantly facilitated in a different neuronal population. The clinically active kainate receptor antagonist LY466195 attenuated trigeminovascular activation in all neurons. In addition, LY466195 demonstrated an N-methyl-d-aspartate receptor-mediated effect. This study demonstrates a differential role of GluK1 receptors in the TCC, antagonism of which can inhibit trigeminovascular activation through postsynaptic mechanisms. Furthermore, the data suggest a novel, possibly presynaptic, modulatory role of trigeminocervical kainate receptors in vivo. Differential activation of kainate receptors suggests unique roles for this receptor in pro- and antinociceptive mechanisms in migraine pathophysiology.

Olvanil acts on transient receptor potential vanilloid channel 1 and cannabinoid receptors to modulate neuronal transmission in the trigeminovascular system.

The transient receptor potential vanilloid channel 1 (TRPV1) is a nociceptive transducer located on nociceptive neurons. TRPV1 channels located on peripheral neurons mainly transduce the sense of heat and are also activated by low pH or capsaicin. The role of centrally located TRPV1 channels is not fully understood. Likewise their importance in pain syndromes of central origin, such as migraine, is not known. Experimental data suggest a relationship to migraine. However, experimental studies with TRPV1 receptor antagonists indicate that the receptor may not be a useful target for new acute migraine treatments. Any potential role for the receptor in the chronification of migraine has not been investigated. The present study aimed at analyzing the use of the TRPV1 channel as a target to desensitize trigeminal neurons and thereby inhibit neuronal activity in the trigeminocervical complex. The TRPV1 receptor agonist olvanil was used for desensitization because, as compared with capsaicin, it is non-noxious and lacks capsaicin's pungency and CGRP release potential. We further investigated a possible effect of olvanil on cannabinoid (CB(1)) receptors, as an interaction between both receptor systems has been described previously. The results show that olvanil dose-dependently inhibited spontaneous and stimulus-induced activity within the trigeminocervical complex, whereas it had no effect on CSD susceptibility. We further demonstrated that the inhibiting effect of olvanil is mediated by vanilloid and cannabinoid receptor systems, thereby using the synergistic effects this dual mechanism offers. Curiously, TRPV1 receptor agonism may have anti-nociceptive properties through central mechanisms that would be of considerable interest to elucidate.

Middle meningeal artery arising from the basilar artery: report of a case and its probable embryological mechanism.

An extremely rare variation of the (left) middle meningeal artery (MMA) originating from the basilar artery, detected incidentally during cerebral angiography, is reported. The right MMA was normal and an accessory meningeal artery arising from the maxillary artery was present on both the sides. The foramen spinosum on the variant side was absent. This abnormal origin of the MMA can be explained by the presence of a perineural arterial network in the region of the Gasserian ganglion, formed by branches of the developing basilar and stapedial arterial systems; the middle meningeal-basilar arterial channel opening up in the absence of a normally developing MMA.

Inhibition of trigeminovascular dural nociceptive afferents by Ca(2+)-activated K(+) (MaxiK/BK(Ca)) channel opening.

Migraine is an episodic brain disorder with a significant morbidity. It is thought that activation of trigeminal afferents innervating the dura mater and large cerebral blood vessels is involved in the expression of the disorder. The selective large conductance calcium-activated potassium channels, the BK(Ca) or MaxiK channels, are intrinsic membrane proteins that are widely distributed in the brain. These channels are thought to be involved in controlling neuronal excitability and perhaps transmitter release, possibly in the trigeminocervical complex. We sought to investigate the role of MaxiK/BK(Ca) channels opening in several models of trigeminovascular nociception using NS1619, a benzimidazolone analogue. Intravenously administered NS1619 (10 mg kg(-1)) was able to inhibit neurogenic dural vasodilation (F(4,20)=19.23, P<0.05, n=6). NS1619 (intravenous) was not able to inhibit Aδ-fiber (F(3.01,18.06)=0.79, P=0.52) or C-fiber (F(3.14,18.84)=0.76, P=0.54) afferents in the trigeminal nucleus caudalis and C(1) region of the dorsal horn after dural electrical stimulation, but it was able to inhibit Aδ-fiber afferents after iontophoretic application of NS1619 (t(5)=3.23, P<0.05, n=6) after 5 min. Iontophoresed NS1619 was also able to inhibit l-glutamate induced firing in the trigeminocervical complex, in a dose-dependent manner (F(3,54)=3.06, P<0.05). The data taken together indicate that the MaxiK/BK(Ca) channel may represent a novel therapeutic target in migraine.

Distribution of artemin and GFRalpha3 labeled nerve fibers in the dura mater of rat: artemin and GFRalpha3 in the dura.

OBJECTIVE: We examined the distribution of artemin and its receptor, glial cell line-derived neurotrophic factor family receptor alpha3 (GFRalpha3), in the dura mater of rats. BACKGROUND: Artemin, a member of the glial cell line-derived neurotrophic factor family, is a vasculature-derived growth factor shown to regulate migration of sympathetic neuroblasts and targeting of sympathetic innervation. The artemin receptor, GFRalpha3, is present in both sympathetic efferents and a subpopulation of nociceptive afferents. Recent evidence has shown that artemin may contribute to inflammatory hyperalgesia. The extent to which artemin is present in the dural vasculature and its relationship to GFRalpha3 containing fibers have yet to be investigated. METHODS: We used retrograde labeling, double and triple labeling with immunohistochemistry on the dura mater and trigeminal ganglia of female Sprague-Dawley rats. RESULTS: Artemin-like immunoreactivity (-LI) was detected in the smooth muscle of dural vasculature. GFRalpha3-LI was present in nerve fibers that closely associated with tyrosine hydroxylase or calcitonin gene-related peptide (CGRP). CGRP-LI and transient receptor potential ion channel 1 (TRPV1)-LI were present in all GFRalpha3-positive dural afferents, which constituted 22% of the total population of dural afferents. CONCLUSIONS: These anatomical results support the hypothesis that artemin contributes to dural afferent activity, and possibly migraine pain, through modulation of both primary afferent and sympathetic systems.

Central projections of the sensory innervation of the rat middle meningeal artery.

Headaches, especially migraine, involve not only pain but also aspects such as vasodilation of cranial vessels and sensitization of nerve endings, processes dependent on and connected to the central nervous system. To understand pathogenic mechanisms of headache, it is important to elucidate the central projections of sensory nerves that innervate cranial vessels, of which the middle meningeal artery (MMA) is the largest artery supplying the dura mater. In this study, cholera toxin subunit b (CTb) or wheat germ agglutinin-horseradish peroxidase conjugate (WGA-HRP) was applied on the adventitia of MMA. After perfusion fixation, the brainstem, the C1-C4 spinal segments and the trigeminal and C2 dorsal root ganglia were removed and sections from these tissues were processed to visualize transported tracers. Labeled cell bodies were seen ipsilaterally in the trigeminal and C2 dorsal root ganglia. Labeled nerve terminations were found ipsilaterally in the lateral part of the spinal dorsal horn of segments C1-C3 and in the caudal and interpolar parts of the spinal trigeminal nucleus. WGA-HRP labeled terminations were mainly located in laminae I and II, whereas CTb labeled terminations located in laminae III-V. These results indicate that sensory information from the MMA is transmitted through both trigeminal and cervical spinal nerve branches to a region in the central nervous system extending rostrally from the C3 dorsal horn to the interpolar part of the spinal trigeminal nucleus. Our data further substantiates that the sensory innervation of the MMA, in addition to putative nociceptive afferents, include a population of large caliber afferents with an as yet unclear but presumably non-nociceptive role.

Feeling and seeing headaches.

The aim is to deepen our understanding of headache by three approaches. First, by trying to feel patients' total experience by eliciting their symptoms in detail, and from their reactions to these experiences. Second, by trying to remember one's own experience of headache, and observing a few patients during different headache types. Third, by attempting to see the different mechanisms of headaches by their sites of origin and their pathophysiology. Migraine, tension-type and cluster headache are the three headaches examined by these approaches. Migraine seems to arise from disturbances of the brain's cortex followed by meningeal pain--hence is intracranial in origin. Tension-type headache seems to arise from extracranial muscles, although the pain derives from the fascia or tendons of those muscles; common sites are the masticatory apparatus and the neck--hence extracranial. Cluster headache remains a mystery although vasodilatation provokes, and vasoconstriction stops, attacks--hence vasomotor control is therapeutically valuable. It is concluded that we need more adventurous ideas to deepen our understanding of these and other headaches.

Orexin 1 receptor activation attenuates neurogenic dural vasodilation in an animal model of trigeminovascular nociception.

The pathophysiology underlying the pulsating quality of the pain of a migraine attack is not fully understood, although trigeminal vascular afferents containing the sensory neuropeptide calcitonin gene-related peptide (CGRP) must have a role. Antimigraine drugs, such as triptans, serotonin 5-hydroxytryptamine(1B/1D) receptor agonists, reproducibly block neurogenic vasodilation associated with CGRP release. We examined the effects of the hypothalamic neuropeptides orexin A and orexin B on neurogenic dural vasodilation, dissecting out the receptor pharmacology with the novel orexin 1 (OX1) receptor antagonist N-(2-methyl-6-benzoxazolyl)-N''-1,5-naphthyridin-4-yl urea (SB-334867). Electrical stimulation of dural afferents (50-300 microA) resulted in reproducible dural vasodilation of 136 +/- 9%. Orexin A 30 microg kg(-1), but not 3 and 10 microg kg(-1), inhibited the dilation brought about by electrical stimulation over 60 min and maximally after 15 min by 60% (t7= 7.138; P < 0.001; n = 8). This response was reversed by pretreatment with the OX1 receptor antagonist SB-334867. Addition of CGRP(8-37) at the point of maximal effect of orexin A produced a further significant decrease in neurogenic dural vasodilation compared with orexin A only. CGRP administration (1 microg kg(-1)) produced a reproducible dural blood vessel dilation of 145 +/- 7% that was not inhibited by intravenous administration of orexin A (30 microg kg(-1)). Orexin B had no significant effect even at the highest dose. The current study demonstrates that orexin A is able to inhibit neurogenic dural vasodilation via activation of the OX1 receptor, resulting in inhibition of prejunctional release of CGRP from trigeminal neurons.

The anatomical relationship between the position of the auriculotemporal nerve and mandibular condyle.

Head, neck, face, and ear pains are commonly associated with disorders of the temporomandibular joint (TMJ). Several theories have been proposed regarding the functional relationship of the TMJ and the associated structures, and how they might contribute to certain painful conditions. This study was conducted to determine the anatomic relationship of the auriculotemporal nerve to the middle meningeal artery and the mandibular condyle. Forty human cadaver temporomandibular joints were dissected to locate the precise position of the auriculotemporal nerve to the mandibular condyle. The study findings revealed a significant variation in the relationship of the auriculotemporal nerve to the middle meningeal artery. The auriculotemporal nerve was found to be between 10-13 mm inferior to the superior surface of the condyle and 1-2 mm posterior to the neck of the condyle. The nerve was not found to be in a position that would likely create an entrapment with adjacent tissues. These findings may assist the clinician to locate the most appropriate injection site for an auriculotemporal nerve block.

The anti-migraine 5-HT(1B/1D) agonist rizatriptan inhibits neurogenic dural vasodilation in anaesthetized guinea-pigs.

These studies investigated the pharmacology of neurogenic dural vasodilation in anaesthetized guinea-pigs. Following introduction of a closed cranial window the meningeal (dural) blood vessels were visualized using intravital microscopy and the diameter constantly measured using a video dimension analyser. Dural blood vessels were constricted with endothelin-1 (3 microg kg(-1), i.v.) prior to dilation of the dural blood vessels with calcitonin gene-related peptide (CGRP; 1 microg kg(-1), i.v.) or local electrical stimulation (up to 300 microA) of the dura mater. In guinea-pigs pre-treated with the CGRP receptor antagonist CGRP((8-37)) (0.3 mg kg(-1), i.v.) the dilator response to electrical stimulation was inhibited by 85% indicating an important role of CGRP in neurogenic dural vasodilation in this species. Neurogenic dural vasodilation was also blocked by the 5-HT(1B/1D) agonist rizatriptan (100 microg kg(-1)) with estimated plasma levels commensurate with concentrations required for anti-migraine efficacy in patients. Rizatriptan did not reverse the dural dilation evoked by CGRP indicating an action on presynaptic receptors located on trigeminal sensory fibres innervating dural blood vessels. In addition, neurogenic dural vasodilation was also blocked by the selective 5-HT(1D) agonist PNU-142633 (100 microg kg(-1)) but not by the 5-HT(1F) agonist LY334370 (3 mg kg(-1)) suggesting that rizatriptan blocks neurogenic vasodilation via an action on 5-HT(1D) receptors located on perivascular trigeminal nerves to inhibit CGRP release. This mechanism may underlie one of the anti-migraine actions of the triptan class exemplified by rizatriptan and suggests that the guinea-pig is an appropriate species in which to investigate the pharmacology of neurogenic dural vasodilation.

Colocalization of CGRP with 5-HT1B/1D receptors and substance P in trigeminal ganglion neurons in rats.

Vasodilatation in the dura mater has been implicated in migraine pathogenesis. Anti-migraine triptan drugs block vasodilatation by binding to 5-HT1B/1D receptors localized on the peripheral sensory terminals and dural blood vessel smooth muscles. Previous studies suggest that calcitonin gene-related peptide (CGRP) released from Adelta-fibres plays a more important role than substance P (SP) released from C-fibres in inducing dural vasodilatation and that one of the antimigraine mechanisms of triptan drugs is inhibiting CGRP release. In the present study, the relationship between CGRP and 5-HT1B/1D receptors, and between CGRP and SP in the trigeminal ganglion neurons in rats was examined by double immunohistochemical staining. CGRP, 5-HT1B, 5-HT1D and SP-positive trigeminal ganglion neurons were all predominantly small and medium-sized. In the trigeminal ganglia, approximately 50% of CGRP-positive neurons were 5-HT1B positive. Similarly, approximately 55% of CGRP-positive neurons were 5-HT1D immunoreactive. Approximately 50% of CGRP-positive neurons were SP-positive, while 93% of SP-positive neurons were CGRP-positive, suggesting that nearly all SP-positive neurons also contain CGRP. The fibre types of the 5-HT1B- and 5-HT1D-positive neurons were further investigated with an antibody against the A-fibre marker 200-kDa neurofilaments (NF200). Approximately 46% of the 5-HT1B-positive and 43% of the 5-HT1D-positive trigeminal ganglion neurons were also NF200 positive, indicating that many A-fibre trigeminal neurons express 5-HT1B or 5-HT1D receptors. These results support the hypothesis that one important action of antimigraine drugs is the inhibition of CGRP release and that Adelta-fibres may play an important role in migraine pathogenesis.

Innervation of the human middle meningeal artery: immunohistochemistry, ultrastructure, and role of endothelium for vasomotility.

The majority of nerve fibers in the middle meningeal artery and branching arterioles are sympathetic, storing norepinephrine and neuropeptide Y (NPY). A sparse supply of fibers contain acetylcholinesterase activity and immunoreactivity toward vasoactive intestinal peptide (VIP), peptidine histidine methionine (PHM), and calcitonin gene-related peptide (CGRP). Only few substance P and neuropeptide K immunoreactive fibers are noted. Electronmicroscopy shows axons and terminals at the adventitial medial border of the human middle meningeal artery, with a fairly large distance to the smooth muscle cells (>500 nM). Several axon profiles contain vesicles of different types, including putative sensory profiles. The perivascularly stored signal substances, norepinephrine and NPY induced vasoconstrictor. Relaxations were induced by acetylcholine and substance P, and these were significantly reduced in arteries without endothelium, while the responses to norepinephrine, NPY, VIP, PHM, and CGRP were not changed by endothelium removal. Blockade experiments showed that the vasomotor responses to norepinephrine were blocked by prazosin, to NPY by BIBP 3226, acetylcholine by atropin, substance P by RP 67580, and the human alpha-CGRP response by human alpha-CGRP(8-37).

The distribution of the auriculotemporal nerve around the temporomandibular joint.

OBJECTIVE: The purpose of this cadaver dissection was to study the position of the auriculotemporal nerve in relation to the mandibular condyle, capsular tissues, articular fossa, and lateral pterygoid muscle and to evaluate the anatomic possibility of nerve impingement or irritation by the surrounding structures. STUDY DESIGN: Eight cadaveric heads (16 sides) were dissected. The auriculotemporal nerve was identified by following its course around the middle meningeal artery. The course of the nerve trunk was dissected from the middle meningeal artery to the terminal branches within the temporomandibular disk. The horizontal distance between the auriculotemporal nerve and the medial portion of the condyle/condylar neck was measured. The vertical distance from the most superior portion of the articular condyle to the superior border of the auriculotemporal nerve was measured. RESULTS: The auriculotemporal nerve was identified on each side, and a single trunk was evident along the medial aspect of the condylar neck. At the posterior border of the lateral pterygoid muscle, the nerve trunk was in direct contact with the condylar neck in every specimen. The average vertical distance between the superior condyle and the nerve was 7.06 mm (+/- 3.21 mm); the range was 0 to 13 mm. The vertical distance between the nerve and the superior condyle on one side of the specimen did not correlate with the distance on the contralateral side. CONCLUSION: The auriculotemporal nerve trunk has a close anatomic relationship with the condyle and the temporomandibular joint capsular region, and there is evidence of a possible mechanism for sensory disturbances in the temporomandibular joint region. In all cases, the nerve was in direct contact with the medial aspect of the capsule or condylar neck. Because there is no correlation between the positions of the nerves on the right and left sides, only one side may be affected. The nerve was also observed to course in direct apposition to the lateral pterygoid muscle. The findings support the hypothesis that the anatomic and clinical relationship of the auriculotemporal nerve to the condyle, articular fossa, and lateral pterygoid muscle may be causally related to compression or irritation of the nerve, producing numbness or pain, or both, in the temporomandibular joint region.

Sympathetic and sensory innervation of the extracerebral vasculature: roles for p75NTR neuronal expression and nerve growth factor.

The extracerebral vasculature receives a postnatal innervation of noradrenergic sympathetic axons and nociceptive sensory axons. These axons are responsive to the neurotrophin nerve growth factor (NGF), in that they possess the transmembrane receptors p140proto-trkA and p75neurotrophin receptor (NTR) which bind NGF. p75NTR-deficient mice display reduced patterns of sympathetic innervation of the pineal gland and sensory innervation of the skin (Lee et al., 1992, 1994a). The goal of this investigation was to determine whether an absence of p75 expression likewise perturbs the sympathetic and sensory innervation of the extracerebral vessels of adult mice, and if so, whether increasing levels of NGF within the target field is capable of enhancing this perturbed axon growth. Four lines of mice were used: wild-type C57Bl/6 mice, transgenic mice overexpressing NGF in the brain, p75NTR-deficient mice, and hybrid mice which overexpress NGF in the brain but lack p75NTR expression. Sympathetic and sensory innervation of the meningeal arteries were severely perturbed in p75NTR-deficient mice. Wild-type and hybrid mice displayed comparable patterns of sympathetic and sensory axons along the dural arteries. Transgenic mice, however, possessed the greatest degree of arterial innervation. These data reveal that while p75NTR expression may be a critical factor for initiating axon growth along the extracerebral vasculature during postnatal development, the sympathetic and sensory nervous systems display a remarkable degree of NGF-induced axonal plasticity, such that increased levels of NGF can ameliorate perturbed patterns of arterial innervation in p75-deficient mice.

Weakness of sympathetic neural control of human pial compared with superficial temporal arteries reflects low innervation density and poor sympathetic responsiveness.

BACKGROUND AND PURPOSE: The primary goal of these studies was to understand and investigate the capacity of perivascular nerves to influence the tone of human pial arteries and to compare them with other human cephalic arteries, the superficial temporal and middle meningeal. METHODS: Responses to electrical activation of intramural nerves and related features of fresh segments of human cephalic arteries-the pial (PA; 478+/-34 microm ID), middle meningeal (MMA; 540+/-41 microm ID), and superficial temporal (STA; 639+/-49 microm ID)-obtained from patients aged 15 to 82 years during surgical procedures were studied on a resistance artery myograph. RESULTS: The PA segment responses to electrical nerve activation and to norepinephrine (NE; 10[-5] mol/L) were 1% and 21% of tissue maximum, respectively, compared with 6% and 34% for the MMA and 14% and 90% for the STA. Tissue maximum was defined as the force increase to 127 mmol/L KCl plus arginine vasopressin (1 microm). All arteries dilated well to acetylcholine. Possible explanations for the PA marginal neurogenic responses were assessed. NE ED50 was 5.4+/-2.2 X 10(-7) mol/L and did not vary with age or diameter. NE responsiveness did not increase in vessels with spontaneous or raised potassium-induced tone. Relaxation to isoproterenol was variable and propranolol did not increase the neurogenic response. Neither N(G)-monomethyl-L-arginine, N(G)-nitro-L-arginine methyl ester, endothelium removal, nor indomethacin consistently influenced the contractions to NE or neurogenic reactivity. The weak PA neurogenic response is in keeping with its poor innervation. As determined by catecholamine histofluorescence, innervation in the PA is sparse, with density increasing in the order PA, MMA, and STA. The incidence of nerve structures in the PA adventitio-medial junction was only 3% of those in the STA, and these were situated more than 3 microm from the closest smooth muscle cell. CONCLUSIONS: We conclude that the weak neurogenic response of adult human pial artery reflects its poor innervation and responsiveness to NE, implying that these features are not important in the regulation of its diameter.

[Innervation of human pia mater arteries of different diameters in arteriosclerosis]. / Innervatsiia pial'nykh arterii raznogo diametra cheloveka pri ateroskleroze.

Scanning electron microscopy, impregnation, histochemical methods with acetylcholine esterase (AChE), choline acetyltransferase and glyoxylic acid were used for studying elements of afferent and efferent (+ adrenergic and cholinergic) innervation of pial arteries 450-60 microns in diameter in persons with "preclinical" atherosclerosis. Marked changes of the nervous system were found in arteries of large calibre. Disorders were seen in afferent innervation with increased crimp in nervous fibers, alternate patches of hypo- and hyperimpregnation, thickening with a high AChE activity, reactive changes in receptors. The structure of choline- and adrenergic nervous plexuses was disordered; the concentration of nervous fibers and varicosities in particular in fluorescent plexuses was decreased, with a moderate increase in the concentration of these structures being seen in cholinergic plexuses.

[Receptor glomeruli and their ultrastructural organization in the arteries and pia mater of the brain and spinal cord of humans]. / Retseptornye klubochki i ikh u'ltrastrukturnaia organizatsiia v arteriiakh i miagkoi obolochke golovnogo i spinnogo mozga cheloveka.

Receptor glomeruli have been studied in the arterial walls of the pia mater of the human brain and spinal cord by means of the light and electron microscopy methods. Zone of their high concentration have been stated; three types of receptor glomeruli have been determined, as well as 3 types of ultrastructural organization of sensitive terminals.

Neuronal pathways to the rat middle meningeal artery revealed by retrograde tracing and immunocytochemistry.

The origin of nerve fibers to the middle meningeal artery of rat was studied by retrograde tracing in combination with immunocytochemistry. Application of the retrograde tracer, True blue (TB), to the middle meningeal artery labeled nerve cell bodies in the ipsilateral superior cervical ganglion, the otic ganglion, the sphenopalatine ganglion, the jugular-nodose ganglionic complex, the trigeminal ganglion and the cervical dorsal root ganglion at level C2. A few nerve cell bodies were labeled in the contralaterally placed ganglia. Judging from the number of labeled nerve cell bodies, the ipsilateral superior cervical ganglion, the otic ganglion, the sphenopalatine and the trigeminal ganglia contribute most to its innervation. A moderate supply of labeled nerve cell bodies was seen in the cervical dorsal root ganglion at level C2 whereas there were only few in the jugular-nodose ganglionic complex. The TB-labeled nerve cell bodies were further examined for the presence of neuropeptides. For that purpose antibodies against neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP) and substance P (SP) were used. Most of the TB-labeled nerve cell bodies in the superior cervical ganglion exhibited NPY-immunoreactivity. In the sphenopalatine and otic ganglia the majority of the TB-labelled neurons were VIP-immunoreactive whereas in the trigeminal and dorsal root ganglion at level C2 the majority of labeled nerve cell bodies displayed CGRP-immunofluorescence and a minority of the labeled nerve cell bodies were substance P-immunoreactive. Together the findings indicate that several ganglia project to the middle meningeal artery of the rat and that many neuropeptides are involved in vasomotor control and in mediation of afferent information.